ID   TNR18_HUMAN             Reviewed;         241 AA.
AC   Q9Y5U5; B1AME1; O95851; Q5U0I4; Q9NYJ9;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   24-JAN-2024, entry version 188.
DE   RecName: Full=Tumor necrosis factor receptor superfamily member 18;
DE   AltName: Full=Activation-inducible TNFR family receptor;
DE   AltName: Full=Glucocorticoid-induced TNFR-related protein;
DE   AltName: CD_antigen=CD357;
DE   Flags: Precursor;
GN   Name=TNFRSF18; Synonyms=AITR, GITR; ORFNames=UNQ319/PRO364;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH TRAF1; TRAF2
RP   AND TRAF3.
RC   TISSUE=Bone marrow;
RX   PubMed=10074428; DOI=10.1016/s0960-9822(99)80093-1;
RA   Gurney A.L., Marsters S.A., Huang R.M., Pitti R.M., Mark D.T.,
RA   Baldwin D.T., Gray A.M., Dowd A.D., Brush A.D., Heldens A.D., Schow A.D.,
RA   Goddard A.D., Wood W.I., Baker K.P., Godowski P.J., Ashkenazi A.;
RT   "Identification of a new member of the tumor necrosis factor family and its
RT   receptor, a human ortholog of mouse GITR.";
RL   Curr. Biol. 9:215-218(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC   TISSUE=T-cell;
RX   PubMed=10037686; DOI=10.1074/jbc.274.10.6056;
RA   Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D.,
RA   Wang S.-X., Kwon B.S.;
RT   "Identification of a novel activation-inducible protein of the tumor
RT   necrosis factor receptor superfamily and its ligand.";
RL   J. Biol. Chem. 274:6056-6061(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Thymus;
RX   PubMed=10836847; DOI=10.1038/sj.cdd.4400670;
RA   Nocentini G., Ronchetti S., Bartoli A., Spinicelli S., Delfino D.,
RA   Brunetti L., Migliorati G., Riccardi C.;
RT   "Identification of three novel mRNA splice variants of GITR.";
RL   Cell Death Differ. 7:408-410(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   PROTEIN SEQUENCE OF 26-40.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
CC   -!- FUNCTION: Receptor for TNFSF18. Seems to be involved in interactions
CC       between activated T-lymphocytes and endothelial cells and in the
CC       regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B
CC       activation via the TRAF2/NIK pathway.
CC   -!- SUBUNIT: Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6.
CC       Binds through its C-terminus to SIVA1/SIVA.
CC   -!- INTERACTION:
CC       Q9Y5U5; Q9UNG2: TNFSF18; NbExp=2; IntAct=EBI-3962532, EBI-15672281;
CC       Q9Y5U5-2; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12197205, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9Y5U5-1; Sequence=Displayed;
CC       Name=2; Synonyms=GITR-D;
CC         IsoId=Q9Y5U5-2; Sequence=VSP_006508;
CC       Name=3;
CC         IsoId=Q9Y5U5-3; Sequence=VSP_041021;
CC   -!- TISSUE SPECIFICITY: Expressed in lymph node, peripheral blood
CC       leukocytes and weakly in spleen.
CC   -!- INDUCTION: Up-regulated in peripherical mononuclear cells after antigen
CC       stimulation/lymphocyte activation.
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DR   EMBL; AF125304; AAD22635.1; -; mRNA.
DR   EMBL; AF117297; AAD19694.1; -; mRNA.
DR   EMBL; AF241229; AAF63506.1; -; mRNA.
DR   EMBL; AY358877; AAQ89236.1; -; mRNA.
DR   EMBL; BT019531; AAV38338.1; -; mRNA.
DR   EMBL; BT019532; AAV38339.1; -; mRNA.
DR   EMBL; AL162741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471183; EAW56282.1; -; Genomic_DNA.
DR   EMBL; CH471183; EAW56283.1; -; Genomic_DNA.
DR   EMBL; BC152381; AAI52382.1; -; mRNA.
DR   CCDS; CCDS10.1; -. [Q9Y5U5-1]
DR   CCDS; CCDS30552.1; -. [Q9Y5U5-3]
DR   CCDS; CCDS9.1; -. [Q9Y5U5-2]
DR   RefSeq; NP_004186.1; NM_004195.2. [Q9Y5U5-1]
DR   RefSeq; NP_683699.1; NM_148901.1. [Q9Y5U5-2]
DR   RefSeq; NP_683700.1; NM_148902.1. [Q9Y5U5-3]
DR   PDB; 7KHD; X-ray; 2.96 A; C/D=26-162.
DR   PDB; 7LAW; X-ray; 2.75 A; R/S=26-161.
DR   PDBsum; 7KHD; -.
DR   PDBsum; 7LAW; -.
DR   AlphaFoldDB; Q9Y5U5; -.
DR   SMR; Q9Y5U5; -.
DR   BioGRID; 114312; 14.
DR   DIP; DIP-29883N; -.
DR   IntAct; Q9Y5U5; 3.
DR   STRING; 9606.ENSP00000328207; -.
DR   ChEMBL; CHEMBL3712995; -.
DR   GlyCosmos; Q9Y5U5; 1 site, No reported glycans.
DR   GlyGen; Q9Y5U5; 1 site.
DR   iPTMnet; Q9Y5U5; -.
DR   PhosphoSitePlus; Q9Y5U5; -.
DR   SwissPalm; Q9Y5U5; -.
DR   BioMuta; TNFRSF18; -.
DR   DMDM; 13878830; -.
DR   jPOST; Q9Y5U5; -.
DR   MassIVE; Q9Y5U5; -.
DR   PaxDb; 9606-ENSP00000328207; -.
DR   PeptideAtlas; Q9Y5U5; -.
DR   ProteomicsDB; 86508; -. [Q9Y5U5-1]
DR   ProteomicsDB; 86509; -. [Q9Y5U5-2]
DR   ProteomicsDB; 86510; -. [Q9Y5U5-3]
DR   TopDownProteomics; Q9Y5U5-2; -. [Q9Y5U5-2]
DR   ABCD; Q9Y5U5; 41 sequenced antibodies.
DR   Antibodypedia; 2154; 1287 antibodies from 42 providers.
DR   DNASU; 8784; -.
DR   Ensembl; ENST00000328596.10; ENSP00000328207.6; ENSG00000186891.14. [Q9Y5U5-2]
DR   Ensembl; ENST00000379265.5; ENSP00000368567.5; ENSG00000186891.14. [Q9Y5U5-3]
DR   Ensembl; ENST00000379268.7; ENSP00000368570.2; ENSG00000186891.14. [Q9Y5U5-1]
DR   GeneID; 8784; -.
DR   KEGG; hsa:8784; -.
DR   MANE-Select; ENST00000379268.7; ENSP00000368570.2; NM_004195.3; NP_004186.1.
DR   UCSC; uc001adb.4; human. [Q9Y5U5-1]
DR   AGR; HGNC:11914; -.
DR   CTD; 8784; -.
DR   DisGeNET; 8784; -.
DR   GeneCards; TNFRSF18; -.
DR   HGNC; HGNC:11914; TNFRSF18.
DR   HPA; ENSG00000186891; Tissue enhanced (skin).
DR   MIM; 603905; gene.
DR   neXtProt; NX_Q9Y5U5; -.
DR   OpenTargets; ENSG00000186891; -.
DR   PharmGKB; PA36607; -.
DR   VEuPathDB; HostDB:ENSG00000186891; -.
DR   eggNOG; ENOG502SAN0; Eukaryota.
DR   GeneTree; ENSGT00730000111424; -.
DR   HOGENOM; CLU_1017554_0_0_1; -.
DR   InParanoid; Q9Y5U5; -.
DR   OMA; DTCSCQF; -.
DR   OrthoDB; 4154142at2759; -.
DR   PhylomeDB; Q9Y5U5; -.
DR   TreeFam; TF336151; -.
DR   PathwayCommons; Q9Y5U5; -.
DR   Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR   Reactome; R-HSA-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs).
DR   SignaLink; Q9Y5U5; -.
DR   BioGRID-ORCS; 8784; 13 hits in 1146 CRISPR screens.
DR   GeneWiki; TNFRSF18; -.
DR   GenomeRNAi; 8784; -.
DR   Pharos; Q9Y5U5; Tbio.
DR   PRO; PR:Q9Y5U5; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q9Y5U5; Protein.
DR   Bgee; ENSG00000186891; Expressed in skin of abdomen and 117 other cell types or tissues.
DR   ExpressionAtlas; Q9Y5U5; baseline and differential.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005031; F:tumor necrosis factor receptor activity; TAS:ProtInc.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR   GO; GO:0002687; P:positive regulation of leukocyte migration; IMP:UniProtKB.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd13417; TNFRSF18; 1.
DR   Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1.
DR   InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR   InterPro; IPR022318; TNFR_18.
DR   InterPro; IPR034018; TNFRSF18_N.
DR   PANTHER; PTHR47388; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 18; 1.
DR   PANTHER; PTHR47388:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 18; 1.
DR   PRINTS; PR01968; TNFACTORR18.
DR   SMART; SM00208; TNFR; 1.
DR   Genevisible; Q9Y5U5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Apoptosis; Cell membrane;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Membrane;
KW   Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           26..241
FT                   /note="Tumor necrosis factor receptor superfamily member
FT                   18"
FT                   /id="PRO_0000034595"
FT   TOPO_DOM        26..162
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        163..183
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        184..241
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          34..72
FT                   /note="TNFR-Cys 1"
FT   REPEAT          74..112
FT                   /note="TNFR-Cys 2"
FT   REPEAT          115..153
FT                   /note="TNFR-Cys 3"
FT   REGION          214..241
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        217..241
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        34..49
FT                   /evidence="ECO:0000250"
FT   DISULFID        74..86
FT                   /evidence="ECO:0000250"
FT   DISULFID        81..94
FT                   /evidence="ECO:0000250"
FT   DISULFID        115..134
FT                   /evidence="ECO:0000250"
FT   DISULFID        128..153
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         135..241
FT                   /note="TQFGFLTVFPGNKTHNAVCVPGSPPAEPLGWLTVVLLAVAACVLLLTSAQLG
FT                   LHIWQLRSQCMWPRETQLLLEVPPSTEDARSCQFPEEERGERSAEEKGRLGDLWV ->
FT                   CWRCRRRPKTPEAASSPRKSGASDRQRRRGGWETCGCEPGRPPGPPTAASPSPGAPQAA
FT                   GALRSALGRALLPWQQKWVQEGGSDQRPGPCSSAAAAGPCRRERETQSWPPSSLAGPDG
FT                   VGS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10836847"
FT                   /id="VSP_006508"
FT   VAR_SEQ         194..201
FT                   /note="SQCMWPRE -> K (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10037686"
FT                   /id="VSP_041021"
FT   VARIANT         43
FT                   /note="T -> R (in dbSNP:rs11466676)"
FT                   /id="VAR_052354"
FT   VARIANT         64
FT                   /note="E -> K (in dbSNP:rs11466687)"
FT                   /id="VAR_052355"
FT   VARIANT         83
FT                   /note="D -> N (in dbSNP:rs11466688)"
FT                   /id="VAR_052356"
FT   VARIANT         173
FT                   /note="V -> M (in dbSNP:rs11466693)"
FT                   /id="VAR_052357"
FT   STRAND          40..42
FT                   /evidence="ECO:0007829|PDB:7KHD"
FT   HELIX           44..46
FT                   /evidence="ECO:0007829|PDB:7KHD"
FT   STRAND          65..67
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          69..73
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          79..83
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          88..91
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          98..107
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          109..114
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          123..125
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   HELIX           134..136
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          139..143
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          147..149
FT                   /evidence="ECO:0007829|PDB:7LAW"
FT   STRAND          152..155
FT                   /evidence="ECO:0007829|PDB:7LAW"
SQ   SEQUENCE   241 AA;  26000 MW;  90DC3B4AA7E82CBE CRC64;
     MAQHGAMGAF RALCGLALLC ALSLGQRPTG GPGCGPGRLL LGTGTDARCC RVHTTRCCRD
     YPGEECCSEW DCMCVQPEFH CGDPCCTTCR HHPCPPGQGV QSQGKFSFGF QCIDCASGTF
     SGGHEGHCKP WTDCTQFGFL TVFPGNKTHN AVCVPGSPPA EPLGWLTVVL LAVAACVLLL
     TSAQLGLHIW QLRSQCMWPR ETQLLLEVPP STEDARSCQF PEEERGERSA EEKGRLGDLW
     V
//